Sex-specific pathological response to Traumatic Brain Injury

Abstract: Traumatic brain injury (TBI) is one of leading causes of death in the world; survivors commonly exhibit behavioural changes and neurocognitive defects in the long-term. Following TBI, rapid changes in the neurovascular unit (NVU) occur as the permeability of the blood brain barrier (BBB) increases and cerebral blood flow (CBF) becomes dysregulated. An integral component of the NVU are pericytes which help maintain the integrity of the BBB, which are lost following mTBI resulting in BBB permeability and consequential leakage of blood plasma proteins into the brain parenchyma. After sustaining a TBI, females are more likely to develop persistent symptoms and show greater cognitive impairment than males. Importantly, the underlying causes for the differences in recovery following TBI are not well understood. Here, we investigate sex-specific differences following experimental TBI, by targeting capillary CD31 and Podocalyxin and pericyte PDGFrβ in the lateral cortex of mice with immunohistochemical and immunofluorescent techniques. Using an in vivo central fluid percussion injury (cFPI) model, male and female mice were analysed at day 2, 7 and 30 post-injury and were compared with controls. Our findings show that male capillaries and pericytes do not change following cFPI, whereas females showed a response in both capillaries and pericytes. Female mice exhibited reduced capillary width 30 days after cFPI as well as early phase response in pericytes. Our data suggests that sex-specific differences occur in capillaries and in pericytes following cFPI. Further research is required to determine the underlying mechanisms driving sex-specific responses, which may potentially lead to the development of sex-specific therapeutic interventions for TBI.